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Sodium zirconium cyclosilicate API Manufacturers & Suppliers

General Description:

Sodium zirconium cyclosilicate, identified by CAS number 17141-74-1, is a notable compound with significant therapeutic applications. Sodium zirconium cyclosilicate is approved as the trade product Lokelma developed by AstraZeneca - an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension that acts as a highly selective potassium removing agent. It is administered orally and is odorless, tasteless, and stable at room temperature. Approval of the medication is supported by data from three double-blind, placebo-controlled trials and two open-label trials which showed that the onset of action was approximately 1.0 hour and the median time to achieving normal potassium levels in the blood was 2.2 hours, with 92% of patients achieving normal potassium levels within 48 hours following administration. The treatment effect was maintained for up to 12 months.

Indications:

This drug is primarily indicated for: Sodium zirconium cyclosilicate is a potassium binder indicated for the treatment of hyperkalemia in adult patients. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Sodium zirconium cyclosilicate undergoes metabolic processing primarily in: Sodium zirconium cyclosilicate is an inorganic, insoluble compound that is not susceptible to enzymatic metabolism. Additionally, studies have shown it not to be systemically absorbed either. An in vivo mass balance study in rats showed that sodium zirconium cyclosilicate was recovered in the feces with no evidence of systemic absorption. Due to these factors and its insolubility, no _in vivo_ or _in vitro_ studies have thus far been performed to examine its effect on cytochrome P450 (CYP450) enzymes or transporter activity. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Sodium zirconium cyclosilicate are crucial for its therapeutic efficacy: Sodium zirconium cyclosilicate is an inorganic, insoluble compound that is not susceptible to enzymatic metabolism. Additionally, studies have shown it not to be systemically absorbed either. An in vivo mass balance study in rats showed that sodium zirconium cyclosilicate was recovered in the feces with no evidence of systemic absorption. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Route of Elimination:

The elimination of Sodium zirconium cyclosilicate from the body primarily occurs through: Sodium zirconium cyclosilicate is eliminated in the feces. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Pharmacodynamics:

Sodium zirconium cyclosilicate exerts its therapeutic effects through: Sodium zirconium cyclosilicate is capable of reducing serum potassium concentrations as quickly as one hour after ingestion and normokalaemia can be achieved typically within 24 to 48 hours. Sodium zirconium cyclosilicate does not affect serum calcium or magnesium concentrations, or urinary sodium excretion. A close correlation is observed between starting serum potassium levels and effect size; patients with higher starting serum potassium levels have greater reductions in serum potassium. As a consequence of the resultant reduction in serum potassium concentration, there is a reduction in urinary potassium excretion as well. In a study of healthy subjects given sodium zirconium cyclosilicate 5 or 10 grams daily for four days, a dose-dependent reduction in serum potassium concentration and total urinary potassium excretion were accompanied by mean increases in fecal potassium excretion. No statistically significant changes in urinary sodium excretion were observed. Sodium zirconium cyclosilicate has also been observed to bind ammonium in vitro and in vivo, thereby removing ammonium and increasing serum bicarbonate levels. Patients treated with sodium zirconium cyclosilicate were documented as experiencing an increase of 1.1 mmol/L at 5 g once daily, 2.3 mmol/L at 10 g once daily, and 2.6 mmol/L at 15 g once daily in bicarbonate compared with a mean increase of 0.6 mmol/L for the patients receiving placebo. In an environment where other factors affecting renin and aldosterone were not controlled, sodium zirconium cyclosilicate demonstrated a dose-independent reduction in mean serum aldosterone levels (range of -30% to -31%) compared with the placebo group (+14%). No consistent effect on systolic and diastolic blood pressure has yet to be observed. Moreover, mean reductions in blood urea nitrogen (BUN) were observed in the 5 g (-1.1 mg/dL) and 10 g (-2.0 mg/dL) three times daily groups compared with small mean increases in the placebo (0.8 mg/dL) and low dose sodium zirconium cyclosilicate (0.3 mg/dL). The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Sodium zirconium cyclosilicate functions by: Hyperkalemia is a condition defined by elevated potassium levels in the blood, often caused by cardiovascular, renal, and metabolic diseases. Hyperkalemia occurs in 23 to 47% of patients with chronic kidney disease and/or chronic heart failure, and may lead to cardiac arrest and death. Sodium zirconium cyclosilicate is subsequently a non-absorbed, non-polymer inorganic powder with a uniform micropore structure that preferentially captures potassium in exchange for hydrogen and sodium cations. Sodium zirconium cyclosilicate is highly selective for potassium ions, even in the presence of other cations such as calcium and magnesium, _in vitro_. Sodium zirconium cyclosilicate captures potassium throughout the entire gastrointestinal (GI) tract and reduces the concentration of free potassium in the GI lumen, thereby lowering serum potassium levels and increasing fecal potassium excretion to resolve hyperkalemia. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Sodium zirconium cyclosilicate is categorized under the following therapeutic classes: Acids, Acids, Noncarboxylic, Anions, Compounds used in a research, industrial, or household setting, Drugs for Treatment of Hyperkalemia and Hyperphosphatemia, Electrolytes, Gastric Acid Lowering Agents, Ion Exchange Resins, Ions, Laboratory Chemicals, Minerals, Oxides, Oxygen Compounds, Potassium Binder, Potassium-removing Agents, Silicon Compounds. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.